Windfelder, Anton G; Müller, Frank H H; Mc Larney, Benedict; Hentschel, Michael; Böhringer, Anna Christina; von Bredow, Christoph-Rüdiger; Leinberger, Florian H; Kampschulte, Marian; Maier, Lorenz; von Bredow, Yvette M; Flocke, Vera; Merzendorfer, Hans; Krombach, Gabriele A; Vilcinskas, Andreas; Grimm, Jan; Trenczek, Tina E; Flögel, Ulrich (2022). High-throughput screening of caterpillars as a platform to study host-microbe interactions and enteric immunity. Nature communications, 13(1), p. 7216. Nature Publishing Group 10.1038/s41467-022-34865-7
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Mammalian models of human disease are expensive and subject to ethical restrictions. Here, we present an independent platform for high-throughput screening, using larvae of the tobacco hornworm Manduca sexta, combining diagnostic imaging modalities for a comprehensive characterization of aberrant phenotypes. For validation, we use bacterial/chemical-induced gut inflammation to generate a colitis-like phenotype and identify significant alterations in morphology, tissue properties, and intermediary metabolism, which aggravate with disease progression and can be rescued by antimicrobial treatment. In independent experiments, activation of the highly conserved NADPH oxidase DUOX, a key mediator of gut inflammation, leads to similar, dose-dependent alterations, which can be attenuated by pharmacological interventions. Furthermore, the developed platform could differentiate pathogens from mutualistic gastrointestinal bacteria broadening the scope of applications also to microbiomics and host-pathogen interactions. Overall, larvae-based screening can complement mammals in preclinical studies to explore innate immunity and host-pathogen interactions, thus representing a substantial contribution to improve mammalian welfare.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine |
UniBE Contributor: |
Hentschel, Michael |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
28 Nov 2022 11:10 |
Last Modified: |
05 Dec 2022 16:29 |
Publisher DOI: |
10.1038/s41467-022-34865-7 |
PubMed ID: |
36433960 |
BORIS DOI: |
10.48350/175187 |
URI: |
https://boris.unibe.ch/id/eprint/175187 |
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